Cancer is a serious threat to modern society. Malignant cancerous growths, due to their unique characteristics, pose significant challenges for modern medicine. Their characteristics include uncontrollable cell proliferation resulting in unregulated growth of malignant tissue, an ability to invade local and even remote tissues, lack of differentiation, lack of detectable symptoms and most significantly, the lack of effective therapy and prevention.
Cancer can develop in any tissue of any organ or tissue at any age. The etiology of cancer is not clearly defined but mechanisms such as genetic susceptibility, chromosome breakage disorders, viruses, environmental factors and immunologic disorders have all been linked to malignant cell growth and transformation. Cancer encompasses a large category of medical conditions, affecting millions of individuals worldwide. Cancer develops when cells in a part of the body begin to undifferentiate or grow out of control. All cancer types begin with the out-of-control growth of abnormal cells.
There are many types of cancer, including breast, lung, ovarian, bladder, prostate, pancreatic, cervical and leukemia. Currently, some of the main treatments available are surgery, radiation therapy, and chemotherapy. Surgery is often a drastic measure and can have serious consequences. For example, all treatments for ovarian cancer may result in infertility. Some treatments for cervical cancer and bladder cancer may cause infertility and/or sexual dysfunction. Surgical procedures to treat pancreatic cancer may result in partial or total removal of the pancreas and can carry significant risks to the patient. Breast cancer surgery invariably involves removal of part or the entire breast, and in severe cases, surrounding tissue. Some surgical procedures for prostate cancer carry the risk of urinary incontinence and impotence. Surgical procedures for lung cancer patients often give rise to significant post-operative pain, as the ribs must be cut through to access and remove the cancerous lung tissue. In addition, patients who have both lung cancer and another lung disease, such as emphysema or chronic bronchitis, typically experience an increase in their shortness of breath following the surgery.
Radiation therapy has the advantage of killing cancer cells but it also damages non-cancerous tissue at the same time. Chemotherapy involves the administration of various anti-cancer drugs to a patient but often is accompanied by adverse side effects.
Worldwide, more than 10 million people are diagnosed with cancer every year and it is estimated that this number will grow to 15 million new cases every year by 2020. Cancer causes six million deaths every year or 12% of the deaths worldwide. There remains a need for methods that can treat cancer. These methods can provide the basis for pharmaceutical compositions useful in the prevention and treatment of cancer in humans and other mammals.
A series of anti-tumor drugs have been identified. These drugs include nitro and nitroso compounds and their metabolites, which are the subject of U.S. Pat. No. 5,464,871 issued on Nov. 7, 1995 entitled “Aromatic Nitro and Nitroso Compounds and their Metabolites Useful as Anti-viral and Anti-tumor Agents,” U.S. Pat. No. 5,670,518 issued on Sep. 23, 1997 entitled “Aromatic Nitro and Nitroso Compounds and their Metabolites Useful as Anti-viral and Anti-tumor Agents,” U.S. Pat. No. 6,004,978 issued on Dec. 21, 1999 entitled “Methods of Treating Cancer with Aromatic Nitro and Nitroso Compounds and their Metabolites” the disclosures of which are incorporated herein by reference. The use of these compounds has been described in the art as useful in treating mammary gland adenocarcinomas, mammary gland duct carcinomas, lymphocytic leukemia, Kaposi's sarcoma in immunosuppressed patients with AIDS, and neoplastic growths such as non-Hodgkin's lymphoma, and primary lymphomas. However, there is a need to identify additional compounds with anti-tumor activity. Metabolites isolated from precursor compounds provide a source of anti-tumor agents that can be used individually or in combination with other compounds to target various cancerous cells. Metabolites isolated from benzamide precursor compounds provide one such source.